Vinyl chloride-induced interaction of nonalcoholic and toxicant-associated steatohepatitis: Protection by the ALDH2 activator Alda-1

Publication date: Available online 19 April 2019Source: Redox BiologyAuthor(s): Liya Chen, Anna L. Lang, Gavin D. Poff, Wen-Xing Ding, Juliane I. BeierAbstractVinyl chloride (VC), an abundant environmental contaminant causes steatohepatitis at high levels, but is considered safe at lower (i.e., sub-OSHA) levels. However, we have previously shown that even lower VC levels exacerbate experimental nonalcoholic fatty liver disease (NAFLD) caused by high-fat diet (HFD). Mitochondrial oxidative injury and subsequent metabolic dysfunction appeared to play key roles in mediating this interaction. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) serves as a key line of defense against endogenous and exogenous reactive aldehydes. The current study therefore tests the hypothesis that allosteric activation of ALDH2 with Alda-1 will protect against VC-enhanced NAFLD. Mice were exposed to low VC concentrations (<1 ppm), or room air for 6 h/day, 5 days/week for 12 weeks, while on HFD or low-fat control diet (LFD). Some mice received Alda-1 (20 mg/kg i.p., 3 × /week) for the last 3 weeks of diet/VC exposure. Indices of liver injury, oxidative stress, metabolic and mitochondrial (dys)function were measured. As observed previously, low-dose VC did not cause liver injury in control mice; while liver injury caused by HFD was enhanced by VC. VC decreased hepatic ALDH2 activity of mice fed HFD. Alda-1 attenuated oxidative stress, liver injury, and dysmetabolism in mice exposed to HFD+VC un...
Source: Redox Biology - Category: Biology Source Type: research